Targeted therapy of brain ischaemia using Fas ligand antibody conjugated PEG-lipid nanoparticles
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- 作者：Ying-mei Lu ; Ji-yun Huang ; Huan Wang ; Xue-fang Lou ; Mei-hua Liao ; Ling-juan Hong ; Rong-rong Tao ; Muhammad M. Ahmed ; Chun-lei Shan ; Xiao-liang Wang ; Kohji Fukunaga ; Yong-zhong Du ; Feng Han
- 关键词：PEGylated lipid nanoparticles ; Brain-targeted delivery ; Fas ligand ; Brain ischaemia ; 3-n-Butylphthalide
- 刊名：Biomaterials
- 出版年：January, 2014
- 年：2014
- 卷：35
- 期：1
- 页码：530-537
- 全文大小：2739 K
文摘
The translation of experimental stroke research from the laboratory to successful clinical practice remains a formidable challenge. We previously reported that PEGylated-lipid nanoparticles (PLNs) effectively transport across the blood-brain barrier along with less inflammatory responses. In the present study, PLNs conjugated to Fas ligand antibody that selectively present on brain ischaemic region were used for therapeutic targeting. Fluorescent analysis of the mice brain show that encapsulated 3-n-Butylphthalide (dl-NBP) in PLNs conjugated with Fas ligand antibody effectively delivered to ipsilateral region of ischaemic brain. Furthermore, the confocal immunohistochemical study demonstrated that brain-targeted nanocontainers specifically accumulated on OX42 positive microglia cells in ischaemic region of mice model. Finally, dl-NBP encapsulated nano-drug delivery system is resulted in significant improvements in brain injury and in neurological deficit after ischaemia, with the significantly reduced dosages versus regular dl-NBP. Overall, these data suggests that PLNs conjugated to an antibody specific to the Fas ligand constituted an ideal brain targeting drug delivery system for brain ischaemia.